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New Molecular Mechanisms and Advanced Therapies for Solid Tumors
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New Molecular Mechanisms and Advanced Therapies for Solid Tumors

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 9368

Special Issue Editor

Prof. Dr. Valentina De Falco

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Guest Editor
Istituto di Endocrinologia e Oncologia Sperimentale del CNR, Dipartimento di Medicina Molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
Interests: cancer; kinase inhibitor; target therapy; signal transduction; cell cycle; mitogenesis; survival; resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Solid tumors account for approximately 90% of adult human cancers. The two main types of solid tumors are sarcomas and carcinomas.

The current most common solid tumors are breast cancer, lung cancer, prostate cancer, colon cancer and skin cancer. 

Treatment for solid tumors generally combines several types of therapy, which can basically include surgery, chemotherapy, and radiation therapy. With the new understanding of the molecular mechanisms of solid tumor progression, leading to the evolution of many new therapeutic regimens and their subsequent trials, targeted drug therapy, immunotherapy and personalized medicines are now widely employed.

Current precision medicine for solid tumors includes a combination of appropriate cytotoxic agents and targeted drugs for each molecular subtype. Since molecular subtypes provide appropriate therapeutic targets, various molecular subtypes have been explored for gene mutation, gene expression, and protein expression. However, this tumor heterogeneity is considered to be one of the main reasons for chemoresistance, as refractory solid tumors exhibit very high tumor heterogeneity and fail to be eradicated even when treated with different anticancer drugs.

This Special Issue aims to provide a platform for the research on new molecular mechanisms in solid tumors, with particular attention to potential new targets and treatments and therefore to new pathogenetic pathways involved in these diseases. We welcome your submissions of original papers and updated review articles based on findings from a molecular point of view.

Prof. Dr. Valentina De Falco
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • solid tumor
  • kinase inhibitors
  • animal model
  • cell culture
  • drug resistance
  • signal transduction
  • survival
  • cell reprogramming
  • pathways
  • clinical trials
  • target therapy
  • cell cycle
  • cell death inhibiting
  • oncogene
  • precision medicine

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Published Papers (4 papers)

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Research

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14 pages, 3408 KiB  
Article
Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humH2Mab-250 in Human Breast Cancer Xenografts
by Mika K. Kaneko, Hiroyuki Suzuki, Tomokazu Ohishi, Takuro Nakamura, Miyuki Yanaka, Tomohiro Tanaka and Yukinari Kato
Int. J. Mol. Sci. 2025, 26(3), 1079; https://doi.org/10.3390/ijms26031079 - 26 Jan 2025
Viewed by 999
Abstract
Monoclonal antibody (mAb) and cell-based immunotherapies represent cutting-edge strategies for cancer treatment. However, safety concerns persist due to the potential targeting of normal cells that express reactive antigens. Therefore, it is crucial to develop cancer-specific mAbs (CasMabs) that can bind to cancer-specific antigens [...] Read more.
Monoclonal antibody (mAb) and cell-based immunotherapies represent cutting-edge strategies for cancer treatment. However, safety concerns persist due to the potential targeting of normal cells that express reactive antigens. Therefore, it is crucial to develop cancer-specific mAbs (CasMabs) that can bind to cancer-specific antigens and exhibit antitumor activity in vivo, thereby reducing the risk of adverse effects. We previously screened mAbs targeting human epidermal growth factor receptor 2 (HER2) and successfully developed a cancer-specific anti-HER2 mAb, H2Mab-250/H2CasMab-2 (mouse IgG1, kappa). In this study, we assessed both the in vitro and in vivo antitumor efficacy of the humanized H2Mab-250 (humH2Mab-250). Although humH2Mab-250 showed lower reactivity to HER2-overexpressed Chinese hamster ovary-K1 (CHO/HER2) and breast cancer cell lines (BT-474 and SK-BR-3) than trastuzumab in flow cytometry, both humH2Mab-250 and trastuzumab showed similar antibody-dependent cellular cytotoxicity (ADCC) against CHO/HER2 and the breast cancer cell lines in the presence of effector splenocytes. In addition, humH2Mab-250 exhibited significant complement-dependent cellular cytotoxicity (CDC) in CHO/HER2 and the breast cancer cell lines compared to trastuzumab. Furthermore, humH2Mab-250 possesses compatible in vivo antitumor effects against CHO/HER2 and breast cancer xenografts with trastuzumab. These findings highlight the distinct roles of ADCC and CDC in the antitumor effects of humH2Mab-250 and trastuzumab and suggest a potential direction for the clinical development of humH2Mab-250 for HER2-positive tumors. Full article
(This article belongs to the Special Issue New Molecular Mechanisms and Advanced Therapies for Solid Tumors)
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14 pages, 2215 KiB  
Article
Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer
by Martin J. Raftery, Alexander Sebastian Franzén, Clarissa Radecke, Abdelhadi Boulifa, Günther Schönrich, Sebastian Stintzing, Jens-Uwe Blohmer and Gabriele Pecher
Int. J. Mol. Sci. 2023, 24(10), 9038; https://doi.org/10.3390/ijms24109038 - 20 May 2023
Cited by 19 | Viewed by 3963
Abstract
There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). Chimeric antigen receptor (CAR) natural killer (NK) cells are a promising alternative to CAR-T cell therapy for cancer. A search for a suitable target in TNBC identified [...] Read more.
There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). Chimeric antigen receptor (CAR) natural killer (NK) cells are a promising alternative to CAR-T cell therapy for cancer. A search for a suitable target in TNBC identified CD44v6, an adhesion molecule expressed in lymphomas, leukemias and solid tumors that is implicated in tumorigenesis and metastases. We have developed a next-generation CAR targeting CD44v6 that incorporates IL-15 superagonist and checkpoint inhibitor molecules. We could show that CD44v6 CAR-NK cells demonstrated effective cytotoxicity against TNBC in 3D spheroid models. The IL-15 superagonist was specifically released upon recognition of CD44v6 on TNBC and contributed to the cytotoxic attack. PD1 ligands are upregulated in TNBC and contribute to the immunosuppressive tumor microenvironment (TME). Competitive inhibition of PD1 neutralized inhibition by PD1 ligands expressed on TNBC. In total, CD44v6 CAR-NK cells are resistant to TME immunosuppression and offer a new therapeutic option for the treatment of BC, including TNBC. Full article
(This article belongs to the Special Issue New Molecular Mechanisms and Advanced Therapies for Solid Tumors)
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Review

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30 pages, 3569 KiB  
Review
Understanding Neovascularization in Glioblastoma: Insights from the Current Literature
by Mariagiovanna Ballato, Emanuela Germanà, Gabriele Ricciardi, Walter Giuseppe Giordano, Pietro Tralongo, Mariachiara Buccarelli, Giorgia Castellani, Lucia Ricci-Vitiani, Quintino Giorgio D’Alessandris, Giuseppe Giuffrè, Cristina Pizzimenti, Vincenzo Fiorentino, Valeria Zuccalà, Antonio Ieni, Maria Caffo, Guido Fadda and Maurizio Martini
Int. J. Mol. Sci. 2025, 26(6), 2763; https://doi.org/10.3390/ijms26062763 - 19 Mar 2025
Viewed by 582
Abstract
Glioblastomas (GBMs), among the most aggressive and resilient brain tumors, characteristically exhibit high angiogenic potential, leading to the formation of a dense yet aberrant vasculature, both morphologically and functionally. With these premises, numerous expectations were initially placed on anti-angiogenic therapies, soon dashed by [...] Read more.
Glioblastomas (GBMs), among the most aggressive and resilient brain tumors, characteristically exhibit high angiogenic potential, leading to the formation of a dense yet aberrant vasculature, both morphologically and functionally. With these premises, numerous expectations were initially placed on anti-angiogenic therapies, soon dashed by their limited efficacy in concretely improving patient outcomes. Neovascularization in GBM soon emerged as a complex, dynamic, and heterogeneous process, hard to manage with the classical standard of care. Growing evidence has revealed the existence of numerous non-canonical strategies of angiogenesis, variously exploited by GBM to meet its ever-increasing metabolic demand and differently involved in tumor progression, recurrence, and escape from treatments. In this review, we provide an accurate description of each neovascularization mode encountered in GBM tumors to date, highlighting the molecular players and signaling cascades primarily involved. We also detail the key architectural and functional aspects characteristic of the GBM vascular compartment because of an intricate crosstalk between the different angiogenic networks. Additionally, we explore the repertoire of emerging therapies against GBM that are currently under study, concluding with a question: faced with such a challenging scenario, could combined therapies, tailored to the patient’s genetic signatures, represent an effective game changer? Full article
(This article belongs to the Special Issue New Molecular Mechanisms and Advanced Therapies for Solid Tumors)
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17 pages, 1034 KiB  
Review
Bladder Epicheck Test: A Novel Tool to Support Urothelial Carcinoma Diagnosis in Urine Samples
by Vincenzo Fiorentino, Cristina Pizzimenti, Mariausilia Franchina, Esther Diana Rossi, Pietro Tralongo, Angela Carlino, Luigi Maria Larocca, Maurizio Martini, Guido Fadda and Francesco Pierconti
Int. J. Mol. Sci. 2023, 24(15), 12489; https://doi.org/10.3390/ijms241512489 - 6 Aug 2023
Cited by 12 | Viewed by 3066
Abstract
Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, [...] Read more.
Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences. Full article
(This article belongs to the Special Issue New Molecular Mechanisms and Advanced Therapies for Solid Tumors)
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